Epigenetic Control of Developmental Processes and Genome Function in Mammals
Our lab focuses on the molecular events governing pre- and post-natal mammalian development. Our research is directed towards investigating the developmental role of imprinted genes and the epigenetic mechanism(s) controlling their parental-origin specific expression and applying this information to understanding epigenetic control and the regulation of developmental processes in a wider context.
Genomic imprinting and parental-orgin effects
Genomic imprinting is a remarkable normal process that causes some genes to be expressed solely from maternally inherited chromosomes and others from paternally inherited chromosomes. This means that the egg and sperm contribute unequal functions to the developing conceptus through the parental-origin specific expression of imprinted genes. In mouse and man, disorders can arise when the dosage of imprinted genes is altered through imbalances in the parental-origin of particular chromosomes, by mutations in the single active allele or by mutations affecting the imprint process. Over the years we and others have contributed to understanding aspects of genomic imprinting including the epigenetic mechanisms that programme functional differences between the two parental chromosomes and generate a heritable memory of parental origin. In addition we have explored the function of imprinted genes in development and disease and the evolution of imprinting and its epigenetic control. Much of our work has focused on the Dlk1-Dio3 imprinted domain on mouse chromosome 12 which contains paternally expressed protein coding genes and multiple non-coding RNAs expressed specifically from the maternally inherited chromosome.
Current research themes
More recently we have been using genomic imprinting as a paradigm for understanding aspects of genome function and its epigenetic control in a wider context. Our current programme is divided into three integrated research themes.
1. Stem cells and the epigenetic programme in vitro and in vivo
2. Functional genomics and epigenomics
3. Development, environment and disease
Selected recent publications
- Charalambous M, Teixeira da Rocha S, Rowland T, Ferron S, Ito M, Radford E, Schuster Gossler K, Hernandez A, Ferguson-Smith A C. Imprinted gene dosage is critical for the transition to independent life. Cell Metabolism15(2) 209-221 (2012).
- Radford E J, Isganaitis E, Jiminez-Chillaron J, Schroeder J, Andrews S, Didier N, Charalambous M, McEwen K, Marazzi G, Sassoon D, Patti M R, Ferguson-Smith A C. An unbiased assessment of the role of imprinted genes in an intergeneration model of developmental programming. PLoS Genetics 8(4) e1002605 (2012).
- Messerschmidt D, DeVries W, Ito M, Solter D, Ferguson-Smith A C, Knowles B B. Trim28 is required for epigenetic stability during oocyte to embryo transition. Science 335(6075) 1499-1452 (2012)
- Ferron S, Charalambous M, Radford E, McEwen K, Wildner H, Hind E, Morante-Redolat J, Laborda J, Guillemot F, Bauer S, Farinas I. Ferguson-Smith A C. Postnatal loss of Dlk1 imprinting in stem cells and niche-astrocytes regulates neurogenesis. Nature 475: 381-385 (2011).